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1. Research considerations for prospective studies of patients with coma and disorders of consciousness

Author

Tinti, Lorenzo, Lawson, Thomas, Molteni, Erika, Kondziella, Daniel, Rass, Verena, Sharshar, Tarek, Bodien, Yelena G, Giacino, Joseph T, Mayer, Stephan A, Amiri, Moshgan, Muehlschlegel, Susanne, Rao, Chethan P Venkatasubba, Vespa, Paul M, Menon, David K, Citerio, Giuseppe, Helbok, Raimund, McNett, Molly, Agarwal, Sachin, Aiyagari, Venkatesh, Akbari, Yama, Albertson, Asher, Alexander, Sheila, Alexandrov, Anne, Alkhachroum, Ayham, Al-Mufti, Fawaz, Amiri, Moshagan, Appavu, Brian, Gebrewold, Meron Awraris, Ayounb, Marc, Badenes, Rafael, Bader, Mary Kay, Badjiata, Neeraj, Balu, Ram, Barlow, Brooke, Barra, Megan, Beekman, Rachel, Beghi, Ettore, Beqiri, Erta, Berlin, Tracey, Bilotta, Federico, Bleck, Thomas, Bodien, Yelena, Boerwinkle, Varina, Boly, Melanie, Bonnel, Alexandra, Brazzi, Luca, Brown, Emery, Bulic, Sebina, Caceres, Eder, Caceres, Adrian, Cafiero, Tullio, Carroll, Elizabeth, Cediel, Emilio G, Chou, Sherry, Claassen, Jan, Condie, Chad, Conti, Alfredo, Cosmas, Katie, Costa, Paolo, Creutzfeldt, Claire, Dangayach, Neha, Dauri, Mario, Debicki, Derek, DeGeorgia, Michael, Der-Nigoghossian, Caroline, Desai, Masoom, Dhar, Rajat, Diringer, Michael, Durr, Emily, Edlow, Brian, Ercole, Ari, Estraneo, Anna, Falcone, Guido, Farrokh, Salia, Ferguson, Adam, Fernandez-Espejo, Davinia, Fink, Ericka, Fins, Joseph, Foreman, Brandon, Franchi, Federico, Frontera, Jennifer, Ganesan, Rishi, Gaspard, Nicolas, Ghavam, Ahmeneh, Giacino, Joseph, Gibbons, Christie, Gilmore, Emily, Glustein, Chavie, Gosseries, Olivia, Green, Theresa, Greer, David, Guanci, Mary, Gupta, Deepak, Hahn, Cecil, Hakimi, Ryan, Hammond, Flora, Hanley, Daniel F, Hartings, Jed, and Hassan, Ahmed

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Neurosciences, Brain Disorders, Prevention, Curing Coma Campaign Collaborators, coma, design, disorders of consciousness, outcomes, prospective studies, Clinical sciences, Biological psychology
Abstract

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilitate a future consensus-based statement (e.g. via a modified Delphi) and series of recommendations. The panel convened weekly online meetings from October 2021 to December 2022. Research considerations addressed the nosographic status of disorders of consciousness, case ascertainment and verification, selection of dependent variables, choice of covariates and measurement and analysis of outcomes and covariates, aiming to promote more homogeneous designs and practices in future observational studies. The goal of this review is to inform a broad community of professionals with different backgrounds and clinical interests to address the methodological challenges imposed by the transition of care from acute to chronic stages and to streamline data gathering for patients with disorders of consciousness. A coordinated effort will be a key to allow reliable observational data synthesis and epidemiological estimates and ultimately inform condition-modifying clinical trials.

Published
2023

3. Diffusion Tensor Imaging Reveals Elevated Diffusivity of White Matter Microstructure that Is Independently Associated with Long-Term Outcome after Mild Traumatic Brain Injury: A TRACK-TBI Study

Author

Palacios, Eva M, Yuh, Esther L, Donald, Christine L Mac, Bourla, Ioanna, Wren-Jarvis, Jamie, Sun, Xiaoying, Vassar, Mary J, Diaz-Arrastia, Ramon, Giacino, Joseph T, Okonkwo, David O, Robertson, Claudia S, Stein, Murray B, Temkin, Nancy, McCrea, Michael A, Levin, Harvey S, Markowitz, Amy J, Jain, Sonia, Manley, Geoffrey T, Mukherjee, Pratik, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Barber, Jason, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Keene, C Dirk, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vespa, Paul, Wang, Kevin, Yue, John K, and Zafonte, Ross

Subjects
Traumatic Head and Spine Injury, Neurosciences, Clinical Research, Traumatic Brain Injury (TBI), Physical Injury - Accidents and Adverse Effects, Brain Disorders, Biomedical Imaging, Injuries and accidents, Neurological, Adolescent, Adult, Brain, Brain Concussion, Brain Injuries, Traumatic, Cohort Studies, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Humans, Middle Aged, White Matter, Young Adult, concussion, diffusion tensor imaging, Glasgow Outcome Scale, MRI, traumatic brain injury, TRACK-TBI Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Diffusion tensor imaging (DTI) literature on single-center studies contains conflicting results regarding acute effects of mild traumatic brain injury (mTBI) on white matter (WM) microstructure and the prognostic significance. This larger-scale multi-center DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI), a cohort study at 11 United States level 1 trauma centers, a total of 391 patients with acute mTBI ages 17 to 60 years were included and studied at two weeks and six months post-injury. Demographically matched friends or family of the participants were the control group (n = 148). Axial diffusivity (AD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were the measures of WM microstructure. The primary outcome was the Glasgow Outcome Scale Extended (GOSE) score of injury-related functional limitations across broad life domains at six months post-injury. The AD, MD, and RD were higher and FA was lower in mTBI versus friend control (FC) at both two weeks and six months post-injury throughout most major WM tracts of the cerebral hemispheres. In the mTBI group, AD and, to a lesser extent, MD decreased in WM from two weeks to six months post-injury. At two weeks post-injury, global WM AD and MD were both independently associated with six-month incomplete recovery (GOSE

Published
2022

4. Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

Author

Mainali, Shraddha, Aiyagari, Venkatesh, Alexander, Sheila, Bodien, Yelena, Boerwinkle, Varina, Boly, Melanie, Brown, Emery, Brown, Jeremy, Claassen, Jan, Edlow, Brian, Fink, Ericka, Fins, Joseph, Foreman, Brandon, Frontera, Jennifer, Geocadin, Romergryko, Giacino, Joseph, Gilmore, Emily, Gosseries, Olivia, Hammond, Flora, Helbok, Raimund, Claude Hemphill, J, Hirsch, Karen, Kim, Keri, Laureys, Steven, Lewis, Ariane, Ling, Geoffrey, Livesay, Sarah, McCredie, Victoria, McNett, Molly, Menon, David, Molteni, Erika, Olson, DaiWai, OPhelan, Kristine, Park, Soojin, Polizzotto, Len, Javier Provencio, Jose, Puybasset, Louis, Venkatasubba Rao, Chethan, Robertson, Courtney, Rohaut, Benjamin, Rubin, Michael, Sharshar, Tarek, Shutter, Lori, Sampaio Silva, Gisele, Smith, Wade, Stevens, Robert, Thibaut, Aurore, Vespa, Paul, Wagner, Amy, Ziai, Wendy, Zink, Elizabeth, and I Suarez, Jose

Subjects
Coma, Curing Coma Campaign, Disorders of consciousness, National Institute of Health, Proceedings, Coma, Consciousness, Consciousness Disorders, Humans, National Institutes of Health (U.S.), United States
Abstract

This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.

Published
2022

5. Consciousness is supported by near-critical slow cortical electrodynamics

Author

Toker, Daniel, Pappas, Ioannis, Lendner, Janna D, Frohlich, Joel, Mateos, Diego M, Muthukumaraswamy, Suresh, Carhart-Harris, Robin, Paff, Michelle, Vespa, Paul M, Monti, Martin M, Sommer, Friedrich T, Knight, Robert T, and D’Esposito, Mark

Subjects
Neurosciences, Clinical Research, Brain Disorders, Epilepsy, Neurodegenerative, 1.1 Normal biological development and functioning, Underpinning research, Animals, Brain Mapping, Cerebral Cortex, Consciousness, Electrophysiological Phenomena, Humans, consciousness, criticality, anesthesia, epilepsy, psychedelics
Abstract

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, we empirically identify a mathematically specific critical point near which waking cortical oscillatory dynamics operate, which is known as the edge-of-chaos critical point, or the boundary between stability and chaos. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magnetoencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of low-frequency cortical electric oscillations away from this critical point; conversely, we show that psychedelics may increase the information richness of cortical activity by tuning low-frequency cortical oscillations closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC) and show that assessing the proximity of slow cortical oscillatory electrodynamics to the edge-of-chaos critical point may be useful as an index of consciousness in the clinical setting.

Published
2022

6. Distribution and volume analysis of early hemorrhagic contusions by MRI after traumatic brain injury: a preliminary report of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx)

Author

La Rocca, Marianna, Barisano, Giuseppe, Bennett, Alexis, Garner, Rachael, Engel, Jerome, Gilmore, Emily J, McArthur, David L, Rosenthal, Eric, Stanis, James, Vespa, Paul, Willyerd, Frederick, Zimmermann, Lara L, Toga, Arthur W, and Duncan, Dominique

Subjects
Psychology, Traumatic Brain Injury (TBI), Physical Injury - Accidents and Adverse Effects, Brain Disorders, Neurosciences, Traumatic Head and Spine Injury, Neurodegenerative, Epilepsy, Biomedical Imaging, Neurological, Brain Injuries, Traumatic, Computational Biology, Contusions, Humans, Magnetic Resonance Imaging, Traumatic brain injury, Lesion segmentation, Posttraumatic late seizures, Lesion volume analysis, EpiBioS4Rx Study Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology, Biomedical and clinical sciences, Health sciences
Abstract

Traumatic brain injury (TBI) can produce heterogeneous injury patterns including a variety of hemorrhagic and non-hemorrhagic lesions. The impact of lesion size, location, and interaction between total number and location of contusions may influence the occurrence of seizures after TBI. We report our methodologic approach to this question in this preliminary report of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx). We describe lesion identification and segmentation of hemorrhagic contusions by early posttraumatic magnetic resonance imaging (MRI). We describe the preliminary methods of manual lesion segmentation in an initial cohort of 32 TBI patients from the EpiBioS4Rx cohort and the preliminary association of hemorrhagic contusion and edema location and volume to seizure incidence.

Published
2021

7. Processed Electroencephalogram-Based Monitoring to Guide Sedation in Critically Ill Adult Patients: Recommendations from an International Expert Panel-Based Consensus

Author

Rasulo, Frank A., Hopkins, Philip, Lobo, Francisco A., Pandin, Pierre, Matta, Basil, Carozzi, Carla, Romagnoli, Stefano, Absalom, Anthony, Badenes, Rafael, Bleck, Thomas, Caricato, Anselmo, Claassen, Jan, Denault, André, Honorato, Cristina, Motta, Saba, Meyfroidt, Geert, Radtke, Finn Michael, Ricci, Zaccaria, Robba, Chiara, Taccone, Fabio S., Vespa, Paul, Nardiello, Ida, and Lamperti, Massimo

Published
2023
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8. Clinical descriptors of disease trajectories in patients with traumatic brain injury in the intensive care unit (CENTER-TBI): a multicentre observational cohort study

Author

Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I.R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Retel Helmrich, Isabel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T.J.M., van Erp, Inge A.M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vande Vyvere, Thijs, van Wijk, Roel P.J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K.W., Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Åkerlund, Cecilia A I, Holst, Anders, Bhattacharyay, Shubhayu, Steyerberg, Ewout, Menon, David K, and Nelson, David W

Published
2024
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9. Statistical Guidelines for Handling Missing Data in Traumatic Brain Injury Clinical Research

Author

Nielson, Jessica L, Cooper, Shelly R, Seabury, Seth A, Luciani, Davide, Fabio, Anthony, Temkin, Nancy R, Ferguson, Adam R, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Jain, Sonia, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Manley, Geoffrey T, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K, Yuh, Esther, and Zafonte, Ross

Subjects
Traumatic Head and Spine Injury, Neurosciences, Brain Disorders, Clinical Research, Traumatic Brain Injury (TBI), Clinical Trials and Supportive Activities, Physical Injury - Accidents and Adverse Effects, Neurological, Injuries and accidents, Good Health and Well Being, Brain Injuries, Traumatic, Child, Data Interpretation, Statistical, Databases, Factual, Guidelines as Topic, Humans, assessment tools, missing data, statistical guidelines, TBI, TRACK-TBI Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Missing data is a persistent and unavoidable problem in even the most carefully designed traumatic brain injury (TBI) clinical research. Missing data patterns may result from participant dropout, non-compliance, technical issues, or even death. This review describes the types of missing data that are common in TBI research, and assesses the strengths and weaknesses of the statistical approaches used to draw conclusions and make clinical decisions from these data. We review recent innovations in missing values analysis (MVA), a relatively new branch of statistics, as applied to clinical TBI data. Our discussion focuses on studies from the International Traumatic Brain Injury Research (InTBIR) initiative project: Transforming Research and Clinical Knowledge in TBI (TRACK-TBI), Collaborative Research on Acute TBI in Intensive Care Medicine in Europe (CREACTIVE), and Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT). In addition, using data from the TRACK-TBI pilot study (n = 586) and the completed clinical trial assessing valproate (VPA) for the treatment of post-traumatic epilepsy (n = 379) we present real-world examples of typical missing data patterns and the application of statistical techniques to mitigate the impact of missing data in order to draw sound conclusions from ongoing clinical studies.

Published
2021

10. Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations

Author

Huie, J Russell, Mondello, Stefania, Lindsell, Christopher J, Antiga, Luca, Yuh, Esther L, Zanier, Elisa R, Masson, Serge, Rosario, Bedda L, Ferguson, Adam R, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Jain, Sonia, Korley, Frederick, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Machamer, Joan, Madden, Christopher, Manley, Geoffrey T, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Schnyer, David, Seabury, Seth, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K, Zafonte, Ross, Ackerlund, Cecilia, Adams, Hadie, Agnoletti, Vanni, Allanson, Judith, Amrein, Krisztina, Andaluz, Norberto, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antun, Azasevac, Antoni, Anna, Ardon, Hilko, Auslands, Kaspars, Azouvi, Philippe, Luisa Azzolini, Maria, Baciu, Camelia, Badenes, Rafael, Bartels, Ronald, Barzó, Pál, Bauerfeind, Ursula, Beauvais, Romuald, Beer, Ronny, Belda, Francisco Javier, Bellander, Bo Michael, Belli, Antonio, Bellier, Rémy, Benali, Habib, Benard, Thierry, Berardino, Maurizio, Beretta, Luigi, Beynon, Christopher, Bilotta, Federico, and Binder, Harald

Subjects
Traumatic Head and Spine Injury, Traumatic Brain Injury (TBI), Neurosciences, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Injuries and accidents, Good Health and Well Being, Biomarkers, Brain Injuries, Traumatic, Common Data Elements, Data Interpretation, Statistical, Humans, Information Dissemination, Reference Standards, biomarkers, data sharing, traumatic brain injury, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators, Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Participants and Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

Published
2021

11. Central Curation of Glasgow Outcome Scale-Extended Data: Lessons Learned from TRACK-TBI

Author

Boase, Kim, Machamer, Joan, Temkin, Nancy R, Dikmen, Sureyya, Wilson, Lindsay, Nelson, Lindsay D, Barber, Jason, Bodien, Yelena G, Giacino, Joseph T, Markowitz, Amy J, McCrea, Michael A, Satris, Gabriela, Stein, Murray B, Taylor, Sabrina R, Manley, Geoffrey T, Adeoye, Opeolu, Bullock, M Ross, Corrigan, John D, Diaz-Arrastia, Ramon, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Gardner, Raquel, Goldman, Dana, Gopinath, Shankar, Hemphill, J Claude, Keene, C Dirk, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Mukherjee, Pratik, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Schnyer, David, Seabury, Seth, Sherer, Mark, Toga, Arthur, Valadka, Alex, Vassar, Mary, MS, RN, Vespa, Paul, Wang, Kevin, Yue, John K, Yuh, Esther, and Zafonte, Ross

Subjects
Traumatic Head and Spine Injury, Traumatic Brain Injury (TBI), Neurosciences, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Quality Education, Adult, Brain Injuries, Traumatic, Disability Evaluation, Female, Functional Status, Glasgow Outcome Scale, Humans, Longitudinal Studies, Male, Middle Aged, Outcome Assessment, Health Care, Recovery of Function, Reproducibility of Results, United States, Young Adult, central review, clinical outcome assessments, data curation, GOSE, traumatic brain injury, TRACK-TBI Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

The Glasgow Outcome Scale (GOS) in its original or extended (GOSE) form is the most widely used assessment of global disability in traumatic brain injury (TBI) research. Several publications have reported concerns about assessor scoring inconsistencies, but without documentation of contributing factors. We reviewed 6801 GOSE assessments collected longitudinally, across 18 sites in the 5-year, observational Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. We recorded error rates (i.e., corrections to a section or an overall rating) based on site assessor documentation and categorized scoring issues, which then informed further training. In cohort 1 (n = 1261; February 2014 to May 2016), 24% of GOSEs had errors identified by central review. In cohort 2 (n = 1130; June 2016 to July 2018), acquired after curation of cohort 1 data, feedback, and further training of site assessors, the error rate was reduced to 10%. GOSE sections associated with the most frequent interpretation and scoring difficulties included whether current functioning represented a change from pre-injury (466 corrected ratings in cohort 1; 62 in cohort 2), defining dependency in the home and community (163 corrections in cohort 1; three in cohort 2) and return to work/school (72 corrections in cohort 1; 35 in cohort 2). These results highlight the importance of central review in improving consistency across sites and over time. Establishing clear scoring criteria, coupled with ongoing guidance and feedback to data collectors, is essential to avoid scoring errors and resultant misclassification, which carry potential to result in "failure" of clinical trials that rely on the GOSE as their primary outcome measure.

Published
2021

12. Invariance of the Bifactor Structure of Mild Traumatic Brain Injury (mTBI) Symptoms on the Rivermead Postconcussion Symptoms Questionnaire Across Time, Demographic Characteristics, and Clinical Groups: A TRACK-TBI Study

Author

Agtarap, Stephanie, Kramer, Mark D, Campbell-Sills, Laura, Yuh, Esther, Mukherjee, Pratik, Manley, Geoffrey T, McCrea, Michael A, Dikmen, Sureyya, Giacino, Joseph T, Stein, Murray B, Nelson, Lindsay D, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Diaz-Arrastia, Ramon, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Jain, Sonia, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K, and Zafonte, Ross

Subjects
Neurosciences, Traumatic Head and Spine Injury, Traumatic Brain Injury (TBI), Clinical Research, Brain Disorders, Physical Injury - Accidents and Adverse Effects, Brain Concussion, Demography, Emotions, Humans, Surveys and Questionnaires, mild TBI, bifactor, invariance, postconcussive symptoms, Rivermead Postconcussion Symptoms Questionnaire, traumatic brain injury, TRACK-TBI Investigators *, Psychology, Clinical Psychology
Abstract

This study aimed to elucidate the structure of the Rivermead Postconcussion Symptoms Questionnaire (RPQ) and evaluate its longitudinal and group variance. Factor structures were developed and compared in 1,011 patients with mild traumatic brain injury (mTBI; i.e., Glasgow Coma Scale score 13-15) from the Transforming Research and Clinical Knowledge in TBI study, using RPQ data collected at 2 weeks, and 3, 6, and 12 months postinjury. A bifactor model specifying a general factor and emotional, cognitive, and visual symptom factors best represented the latent structure of the RPQ. The model evinced strict measurement invariance over time and across sex, age, race, psychiatric history, and mTBI severity groups, indicating that differences in symptom endorsement were completely accounted for by these latent dimensions. While highly unidimensional, the RPQ has multidimensional features observable through a bifactor model, which may help differentiate symptom expression patterns in the future.

Published
2021

14. Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

Author

Claassen, Jan, Akbari, Yama, Alexander, Sheila, Bader, Mary Kay, Bell, Kathleen, Bleck, Thomas P, Boly, Melanie, Brown, Jeremy, Chou, Sherry H-Y, Diringer, Michael N, Edlow, Brian L, Foreman, Brandon, Giacino, Joseph T, Gosseries, Olivia, Green, Theresa, Greer, David M, Hanley, Daniel F, Hartings, Jed A, Helbok, Raimund, Hemphill, J Claude, Hinson, HE, Hirsch, Karen, Human, Theresa, James, Michael L, Ko, Nerissa, Kondziella, Daniel, Livesay, Sarah, Madden, Lori K, Mainali, Shraddha, Mayer, Stephan A, McCredie, Victoria, McNett, Molly M, Meyfroidt, Geert, Monti, Martin M, Muehlschlegel, Susanne, Murthy, Santosh, Nyquist, Paul, Olson, DaiWai M, Provencio, J Javier, Rosenthal, Eric, Sampaio Silva, Gisele, Sarasso, Simone, Schiff, Nicholas D, Sharshar, Tarek, Shutter, Lori, Stevens, Robert D, Vespa, Paul, Videtta, Walter, Wagner, Amy, Ziai, Wendy, Whyte, John, Zink, Elizabeth, Suarez, Jose I, and Curing Coma Campaign

Subjects
Curing Coma Campaign, Biomarkers, Coma, Consciousness, Electrophysiology, Magnetic resonance imaging, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified.

Published
2021

15. Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Author

Nolan, Amber L, Petersen, Cathrine, Iacono, Diego, Mac Donald, Christine L, Mukherjee, Pratik, van der Kouwe, Andre, Jain, Sonia, Stevens, Allison, Diamond, Bram R, Wang, Ruopeng, Markowitz, Amy J, Fischl, Bruce, Perl, Daniel P, Manley, Geoffrey T, Keene, C Dirk, Diaz-Arrastia, Ramon, Edlow, Brian L, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Barber, Jason, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Palacios, Eva, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K, Yuh, Esther, and Zafonte, Ross

Subjects
Biomedical Imaging, Physical Injury - Accidents and Adverse Effects, Acquired Cognitive Impairment, Neurosciences, Traumatic Brain Injury (TBI), Traumatic Head and Spine Injury, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Brain Injuries, Traumatic, Connectome, Diffusion Tensor Imaging, Humans, Male, Middle Aged, Neural Pathways, contusion, MRI, neuropathology, tractography, traumatic axonal injury, traumatic brain injury, TRACK-TBI Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein (APP), loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

Published
2021

16. Validity of the Brief Test of Adult Cognition by Telephone in Level 1 Trauma Center Patients Six Months Post-Traumatic Brain Injury: A TRACK-TBI Study

Author

Nelson, Lindsay D, Barber, Jason K, Temkin, Nancy R, Dams-O'Connor, Kristen, Dikmen, Sureyya, Giacino, Joseph T, Kramer, Mark D, Levin, Harvey S, McCrea, Michael A, Whyte, John, Bodien, Yelena G, Yue, John K, Manley, Geoffrey T, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Diaz-Arrastia, Ramon, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Jain, Sonia, Keene, C Dirk, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Ngwenya, Laura B, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Stein, Murray, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, and Zafonte, Ross

Subjects
Brain Disorders, Traumatic Brain Injury (TBI), Clinical Research, Acquired Cognitive Impairment, Physical Injury - Accidents and Adverse Effects, Traumatic Head and Spine Injury, Behavioral and Social Science, Neurosciences, Mental health, Injuries and accidents, Adult, Brain Injuries, Traumatic, Cognition, Cognition Disorders, Female, Follow-Up Studies, Humans, Male, Mental Recall, Middle Aged, Neuropsychological Tests, Prospective Studies, Reproducibility of Results, Telephone, Time Factors, Trauma Centers, Brief Test of Adult Cognition by Telephone, BTACT, phone-based cognitive assessment, telemedicine, traumatic brain injury, British Neurosurgical Trainee Research Collaborative, Clinical Sciences, Neurology & Neurosurgery
Abstract

Our objective was to examine the construct validity of the Brief Test of Adult Cognition by Telephone (BTACT) and its relationship to traumatic brain injury (TBI) of differing severities. Data were analyzed on 1422 patients with TBI and 170 orthopedic trauma controls (OTC) from the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Participants were assessed at 6 months post-injury with the BTACT and an in-person neuropsychological battery. We examined the BTACT's factor structure, factorial group invariance, convergent and discriminant validity, and relationship to TBI and TBI severity. Confirmatory factor analysis supported both a 1-factor model and a 2-factor model comprising correlated Episodic Memory and Executive Function (EF) factors. Both models demonstrated strict invariance across TBI severity and OTC groups. Correlations between BTACT and criterion measures suggested that the BTACT memory indices predominantly reflect verbal episodic memory, whereas the BTACT EF factor correlated with a diverse range of cognitive tests. Although the EF factor and other BTACT indices showed significant relationships with TBI and TBI severity, some group effect sizes were larger for more comprehensive in-person cognitive tests than the BTACT. The BTACT is a promising, brief, phone-based cognitive screening tool for patients with TBI. Although the BTACT's memory items appear to index verbal Episodic Memory, items that purport to assess EFs may reflect a broader array of cognitive domains. The sensitivity of the BTACT to TBI severity is lower than domain-specific neuropsychological measures, suggesting it should not be used as a substitute for comprehensive, in-person cognitive testing at 6 months post-TBI.

Published
2021

17. Smaller Regional Brain Volumes Predict Posttraumatic Stress Disorder at 3 Months After Mild Traumatic Brain Injury

Author

Stein, Murray B, Yuh, Esther, Jain, Sonia, Okonkwo, David O, Donald, Christine L Mac, Levin, Harvey, Giacino, Joseph T, Dikmen, Sureyya, Vassar, Mary J, Diaz-Arrastia, Ramon, Robertson, Claudia S, Nelson, Lindsay D, McCrea, Michael, Sun, Xiaoying, Temkin, Nancy, Taylor, Sabrina R, Markowitz, Amy J, Manley, Geoffrey T, Mukherjee, Pratik, Investigators, TRACK-TBI, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Barber, Jason, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Keene, C Dirk, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Toga, Arthur, Valadka, Alex, Vespa, Paul, Wang, Kevin, Yue, John K, and Zafonte, Ross

Subjects
Neurosciences, Mental Health, Post-Traumatic Stress Disorder (PTSD), Prevention, Behavioral and Social Science, Anxiety Disorders, Physical Injury - Accidents and Adverse Effects, Traumatic Head and Spine Injury, Brain Disorders, Traumatic Brain Injury (TBI), Clinical Research, Biomedical Imaging, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Mental health, Neurological, Amygdala, Brain, Brain Concussion, Hippocampus, Humans, Stress Disorders, Post-Traumatic, TRACK-TBI Investigators, Cingulate, Insula, PTSD, Posttraumatic stress disorder, TBI, Traumatic brain injury
Abstract

BackgroundBrain volumes in regions such as the hippocampus and amygdala have been associated with risk for the development of posttraumatic stress disorder (PTSD). The objective of this study was to determine whether a set of regional brain volumes, measured by magnetic resonance imaging at 2 weeks following mild traumatic brain injury, were predictive of PTSD at 3 and 6 months after injury.MethodsUsing data from TRACK-TBI (Transforming Research and Clinical Knowledge in TBI), we included patients (N = 421) with Glasgow Coma Scale scores 13-15 assessed after evaluation in the emergency department and at 2 weeks, 3 months, and 6 months after injury. Probable PTSD diagnosis (PTSD Checklist for DSM-5 score, ≥33) was the outcome. FreeSurfer 6.0 was used to perform volumetric analysis of three-dimensional T1-weighted magnetic resonance images at 3T obtained 2 weeks post injury. Brain regions selected a priori for volumetric analyses were insula, hippocampus, amygdala, superior frontal cortex, rostral and caudal anterior cingulate, and lateral and medial orbitofrontal cortices.ResultsOverall, 77 (18.3%) and 70 (16.6%) patients had probable PTSD at 3 and 6 months. A composite volume derived as the first principal component incorporating 73.8% of the variance in insula, superior frontal cortex, and rostral and caudal cingulate contributed to the prediction of 3-month (but not 6-month) PTSD in multivariable models incorporating other established risk factors.ConclusionsResults, while needing replication, provide support for a brain reserve hypothesis of PTSD and proof of principle for how prediction of at-risk individuals might be accomplished to enhance prognostic accuracy and enrich clinical prevention trials for individuals at the highest risk of PTSD following mild traumatic brain injury.

Published
2021

18. Satisfaction with Life after Mild Traumatic Brain Injury: A TRACK-TBI Study

Author

Agtarap, Stephanie D, Campbell-Sills, Laura, Jain, Sonia, Sun, Xiaoying, Dikmen, Sureyya, Levin, Harvey, McCrea, Michael A, Mukherjee, Pratik, Nelson, Lindsay D, Temkin, Nancy, Yuh, Esther L, Giacino, Joseph T, Manley, Geoffrey T, Stein, Murray B, Adeoye, Opeolu, Boase, Kim, Bullock, M Ross, Corrigan, John D, Diaz-Arrastia, Ramon, Ellenbogen, Richard, Ferguson, Adam R, Gardner, Raquel, Goldman, Dana, Gopinath, Shankar, Hemphill, J Claude, Korley, Frederick K, Kreitzer, Natalie, Machamer, Joan, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K, and Zafonte, Ross

Subjects
Traumatic Head and Spine Injury, Neurosciences, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Clinical Research, Traumatic Brain Injury (TBI), Injuries and accidents, Adult, Biomedical Research, Brain Concussion, Chronic Pain, Female, Follow-Up Studies, Humans, Male, Mental Disorders, Middle Aged, Patient Satisfaction, Prospective Studies, Sleep Initiation and Maintenance Disorders, Young Adult, concussion, life satisfaction, post-concussive symptoms, traumatic brain injury, well-being, TRACK-TBI Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Identifying the principal determinants of life satisfaction following mild TBI (mTBI) may inform efforts to improve subjective well-being in this population. We examined life satisfaction among participants in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study who presented with mTBI (Glasgow Coma Scale [GCS] score = 13-15; n = 1152). An L1-regularization path algorithm was used to select optimal sets of baseline and concurrent symptom measures for prediction of scores on the Satisfaction with Life Scale (SWLS) at 2 weeks and 3, 6, and 12 months post-injury. Multi-variable linear regression models (all n = 744-894) were then fit to evaluate associations between the empirically selected predictors and SWLS scores at each follow-up visit. Results indicated that emotional post-TBI symptoms (all b = -1.27 to -0.77, all p

Published
2021

19. Comparative effectiveness of decompressive craniectomy versus craniotomy for traumatic acute subdural hematoma (CENTER-TBI): an observational cohort study

Author

Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubović, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I.R., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Nair, Nandesh, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Oresic, Matej, Ortolano, Fabrizio, Otesile, Olubukola, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rehorčíková, Veronika, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Kowark, Ana, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolijn, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, Van der Jagt, Mathieu, van der Naalt, Joukje, Van der Steen, Gregory, van Dijck, Jeroen T.J.M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Van Veen, Ernest, van Wijk, Roel, Vyvere, Thijs Vande, Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K.W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Ziverte, Agate, Zoerle, Tommaso, van Erp, Inge A.M., Lingsma, Hester F., Pisică, Dana, Yue, John K., Singh, Ranjit D., Kolias, Angelos, Peppel, Lianne D., Heijenbrok-Kal, Majanka, Ribbers, Gerard M., Menon, David K., Hutchinson, Peter J.A., Manley, Geoffrey T., de Ruiter, Godard C.W., and Peul, Wilco C.

Published
2023
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20. Point-of-Care Platform Blood Biomarker Testing of Glial Fibrillary Acidic Protein versus S100 Calcium-Binding Protein B for Prediction of Traumatic Brain Injuries: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

Author

Okonkwo, David O, Puffer, Ross C, Puccio, Ava M, Yuh, Esther L, Yue, John K, Diaz-Arrastia, Ramon, Korley, Frederick K, Wang, Kevin KW, Sun, Xiaoying, Taylor, Sabrina R, Mukherjee, Pratik, Markowitz, Amy J, Jain, Sonia, Manley, Geoffrey T, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, Ross, Chesnut, Randall, Corrigan, John, Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, Venkata, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, Claude, Hotz, Gillian, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Palacios, Eva, Perl, Daniel, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, and Zafonte, Ross

Subjects
Brain Disorders, Clinical Research, Physical Injury - Accidents and Adverse Effects, Traumatic Brain Injury (TBI), Traumatic Head and Spine Injury, Neurosciences, Injuries and accidents, Good Health and Well Being, Adult, Aged, Biomarkers, Brain Injuries, Traumatic, Cohort Studies, Female, Glial Fibrillary Acidic Protein, Humans, Male, Middle Aged, Point-of-Care Systems, S100 Calcium Binding Protein beta Subunit, Sensitivity and Specificity, biomarkers, glial fibrillary acidic protein, S100 calcium-binding protein B, traumatic brain injury, Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13-15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3-15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3-15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472-3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26-397) or orthopedic trauma controls (n = 122; median = 13 pg/mL, IQR: 7-20), p

Published
2020

21. Life After Mild Traumatic Brain Injury: Widespread Structural Brain Changes Associated With Psychological Distress Revealed With Multimodal Magnetic Resonance Imaging

Author

Adeoye, Opeolu, Badjatia, Neeraj, Bodien, Yelena, Bullock, M. Ross, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V. Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J. Claude, Hotz, Gillian, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, Merchant, Randall, Ngwenya, Laura B., Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K., Zafonte, Ross, Sibilia, Francesca, Custer, Rachel M., Irimia, Andrei, Sepehrband, Farshid, Toga, Arthur W., and Cabeen, Ryan P.

Published
2023
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22. Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study

Author

Lutkenhoff, Evan S, Shrestha, Vikesh, Tejeda, Jesus Ruiz, Real, Courtney, McArthur, David L, Duncan, Dominique, La Rocca, Marianna, Garner, Rachael, Toga, Arthur W, Vespa, Paul M, and Monti, Martin M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Traumatic Head and Spine Injury, Neurosciences, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Epilepsy, Neurodegenerative, Clinical Research, Traumatic Brain Injury (TBI), Neurological, Adult, Brain Contusion, Brain Hemorrhage, Traumatic, Brain Injuries, Traumatic, Cerebral Cortical Thinning, Clinical Decision Rules, Computational Biology, Electroencephalography, Epilepsy, Post-Traumatic, Female, Frontal Lobe, Glasgow Coma Scale, Hippocampus, Humans, Image Processing, Computer-Assisted, Logistic Models, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Prospective Studies, Temporal Lobe, Time Factors, Young Adult, traumatic brain injury, epilepsy, MRI, EpiBioS4Rx Study Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundTraumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not.DesignMulticentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI).ResultsFrom a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy.Conclusions and relevanceAlthough this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.

Published
2020

23. The subcortical basis of outcome and cognitive impairment in TBI: A longitudinal cohort study.

Author

Lutkenhoff, Evan S, Wright, Matthew J, Shrestha, Vikesh, Real, Courtney, McArthur, David L, Buitrago-Blanco, Manuel, Vespa, Paul M, and Monti, Martin M

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Physical Injury - Accidents and Adverse Effects, Behavioral and Social Science, Rare Diseases, Acquired Cognitive Impairment, Traumatic Head and Spine Injury, Neurodegenerative, Traumatic Brain Injury (TBI), Basic Behavioral and Social Science, Brain Disorders, Clinical Research, Mental health, Neurological, Good Health and Well Being, Adult, Aged, Attention, Brain, Brain Injuries, Traumatic, Cognitive Dysfunction, Cohort Studies, Executive Function, Female, Follow-Up Studies, Glasgow Coma Scale, Glasgow Outcome Scale, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory, Episodic, Middle Aged, Neuropsychological Tests, Stroop Test, Young Adult, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at 6 months after injury.MethodsFor this longitudinal analysis, clinical and MRI data were collected in a tertiary neurointensive care setting in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient, we collected T1- and T2-weighted MRI data acutely and at the 6-month follow-up, as well as acute measures of injury severity (Glasgow Coma Scale), follow-up measures of functional impairment (Glasgow Outcome Scale-extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.ResultsIn the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first 6 months after injury across the brain. However, only atrophy within subcortical regions, particularly in the left thalamus, was associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good from bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could achieve only 20% accuracy.ConclusionDespite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute event and the longer-term disease of traumatic brain injury.

Published
2020

26. The Curing Coma Campaign: Framing Initial Scientific Challenges—Proceedings of the First Curing Coma Campaign Scientific Advisory Council Meeting

Author

Provencio, J Javier, Hemphill, J Claude, Claassen, Jan, Edlow, Brian L, Helbok, Raimund, Vespa, Paul M, Diringer, Michael N, Polizzotto, Len, Shutter, Lori, Suarez, Jose I, Stevens, Robert D, Hanley, Daniel F, Akbari, Yama, Bleck, Thomas P, Boly, Melanie, Foreman, Brandon, Giacino, Joseph T, Hartings, Jed A, Human, Theresa, Kondziella, Daniel, Ling, Geoffrey SF, Mayer, Stephan A, McNett, Molly, Menon, David K, Meyfroidt, Geert, Monti, Martin M, Park, Soojin, Pouratian, Nader, Puybasset, Louis, Rohaut, Benjamin, Rosenthal, Eric S, Schiff, Nicholas D, Sharshar, Tarek, Wagner, Amy, Whyte, John, and Olson, DaiWai M

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Brain Disorders, Good Health and Well Being, Advisory Committees, Biomarkers, Clinical Trials as Topic, Coma, Consciousness Disorders, Critical Care, Humans, Implementation Science, Neurological Rehabilitation, Neurology, Proof of Concept Study, Stakeholder Participation, Endotype, Biomarker, Consciousness, Recovery, Neurocritical Care Society Curing Coma Campaign, Clinical Sciences, Neurosciences, Neurology & Neurosurgery, Clinical sciences, Nursing
Abstract

Coma and disordered consciousness are common manifestations of acute neurological conditions and are among the most pervasive and challenging aspects of treatment in neurocritical care. Gaps exist in patient assessment, outcome prognostication, and treatment directed specifically at improving consciousness and cognitive recovery. In 2019, the Neurocritical Care Society (NCS) launched the Curing Coma Campaign in order to address the "grand challenge" of improving the management of patients with coma and decreased consciousness. One of the first steps was to bring together a Scientific Advisory Council including coma scientists, neurointensivists, neurorehabilitationists, and implementation experts in order to address the current scientific landscape and begin to develop a framework on how to move forward. This manuscript describes the proceedings of the first Curing Coma Campaign Scientific Advisory Council meeting which occurred in conjunction with the NCS Annual Meeting in October 2019 in Vancouver. Specifically, three major pillars were identified which should be considered: endotyping of coma and disorders of consciousness, biomarkers, and proof-of-concept clinical trials. Each is summarized with regard to current approach, benefits to the patient, family, and clinicians, and next steps. Integration of these three pillars will be essential to the success of the Curing Coma Campaign as will expanding the "curing coma community" to ensure broad participation of clinicians, scientists, and patient advocates with the goal of identifying and implementing treatments to fundamentally improve the outcome of patients.

Published
2020

27. Monitoring Outcome after Hospital-Presenting Milder Spectrum Pediatric Traumatic Brain Injury Using the Glasgow Outcome Scale-Extended, Pediatric Revision

Author

Evans, Emily, Cook, Nathan E, Iverson, Grant L, Townsend, Elise L, Duhaime, Ann-Christine, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M Ross, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Jain, Sonia, Korley, Frederick K, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Manley, Geoffrey T, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John K, Yuh, Esther, and Zafonte, Ross

Subjects
Physical Injury - Accidents and Adverse Effects, Traumatic Head and Spine Injury, Pediatric, Neurosciences, Clinical Research, Traumatic Brain Injury (TBI), Childhood Injury, Unintentional Childhood Injury, Brain Disorders, Injuries and accidents, Adolescent, Brain Concussion, Child, Child, Preschool, Female, Follow-Up Studies, Glasgow Outcome Scale, Hospitalization, Humans, Longitudinal Studies, Male, Recovery of Function, Treatment Outcome, brain concussion, brain injuries, traumatic, head injuries, closed, outcome assessment, pediatrics, TRACK-TBI Investigators, brain injuries, traumatic, head injuries, closed, Clinical Sciences, Neurology & Neurosurgery
Abstract

The Glasgow Outcome Scale, Pediatric Revision (GOSE-P) is an assessment of "global outcome" designed as a developmentally appropriate version of the Glasgow Outcome Scale-Extended for use in clinical trials of children with traumatic brain injury (TBI). Initial testing describes validity across a wide age and injury severity spectrum, yet the GOSE-P's utility for monitoring children with milder injuries is less clear. We examined the level of agreement between the GOSE-P and the Health and Behavior Inventory (HBI), a TBI-related symptom checklist used to assess children with mild TBI for clinical and research purposes. Participants included children and adolescents 3-16 years of age (n = 50) who presented to two level 1 trauma centers within 24 h of injury, with a GCS of 13-15, who underwent clinical neuroimaging. Outcome was assessed 2 weeks and 3 months following injury. We examined the severity of TBI-related symptoms across disability categories identified using the GOSE-P, and the level of agreement between the two measures in identifying deficits 2 weeks following injury and improvement from 2 weeks to 3 months. Using the GOSE-P, 62% had deficits at 2 weeks, and 42% improved from 2 weeks to 3 months. Agreement between the GOSE-P and HBI was fair 2 weeks after TBI (k = 0.24-0.33), and poor for identifying subsequent improvement (k = 0.10-0.16). Modest agreement between the GOSE-P and the HBI may reflect restricted participation from diverse causes, including TBI, other bodily injuries, and prescribed activity restrictions, and highlights the need for multi-dimensional outcome batteries.

Published
2020

28. Alternative substrate metabolism depends on cerebral metabolic state following traumatic brain injury

Author

Greco, Tiffany, Vespa, Paul M, and Prins, Mayumi L

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Traumatic Head and Spine Injury, Traumatic Brain Injury (TBI), Physical Injury - Accidents and Adverse Effects, Brain Disorders, Neurological, Affordable and Clean Energy, 3-Hydroxybutyric Acid, Animals, Brain Injuries, Traumatic, Cerebral Cortex, Energy Metabolism, Female, Glucose, Lactic Acid, Male, Random Allocation, Rats, Rats, Sprague-Dawley, Sex Characteristics, Traumatic brain injury, Alternative substrate, Metabolism, Mitochondria, Sex, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Decreases in energy metabolism following traumatic brain injury (TBI) are attributed to impairment of glycolytic flux and oxidative phosphorylation. Glucose utilization post-TBI is decreased while administration of alternative substrates has been shown to be neuroprotective. Changes in energy metabolism following TBI happens in two phases; a period of hyper-metabolism followed by prolonged hypo-metabolism. It is not understood how different cerebral metabolic states may impact substrate metabolism and ultimately mitochondrial function. Adult male or female Sprague Dawley rats were given sham surgery or controlled cortical impact (CCI) and were assigned one of two administration schemes. Glucose, lactate or beta-hydroxybutyrate (BHB) were infused i.v. either starting immediately after injury or beginning 6 h post-injury for 3 h to reflect the hyper- and hypo-metabolic stages. Animals were euthanized 24 h post-injury. The peri-contusional cortex was collected and assayed for mitochondrial respiration peroxide production, and citrate synthase activity. Tissue acetyl-CoA, ATP, glycogen and HMGB1 were also quantified. Sex differences were observed in injury pattern. Administration based on cerebral metabolic state identified that only early lactate and late BHB improved mitochondrial function and peroxide production and TCA cycle intermediates in males. In contrast, both early and late BHB had deleterious effects on all aspects of metabolic measurements in females. These data stress there is no one optimal alternative substrate, but rather the fuel type used should be guided by both cerebral metabolic state and sex.

Published
2020

29. A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Author

Chesnut, Randall, Aguilera, Sergio, Buki, Andras, Bulger, Eileen, Citerio, Giuseppe, Cooper, D Jamie, Arrastia, Ramon Diaz, Diringer, Michael, Figaji, Anthony, Gao, Guoyi, Geocadin, Romer, Ghajar, Jamshid, Harris, Odette, Hoffer, Alan, Hutchinson, Peter, Joseph, Mathew, Kitagawa, Ryan, Manley, Geoffrey, Mayer, Stephan, Menon, David K, Meyfroidt, Geert, Michael, Daniel B, Oddo, Mauro, Okonkwo, David, Patel, Mayur, Robertson, Claudia, Rosenfeld, Jeffrey V, Rubiano, Andres M, Sahuquillo, Juan, Servadei, Franco, Shutter, Lori, Stein, Deborah, Stocchetti, Nino, Taccone, Fabio Silvio, Timmons, Shelly, Tsai, Eve, Ullman, Jamie S, Vespa, Paul, Videtta, Walter, Wright, David W, Zammit, Christopher, and Hawryluk, Gregory WJ

Subjects
Algorithm, Brain injury, Brain oxygen, Consensus, Head trauma, Intracranial pressure, PbtO2, Protocol, SIBICC, Seattle, Tiers, Emergency & Critical Care Medicine, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundCurrent guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.MethodsOur consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.ResultsWe established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.ConclusionsThese protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.

Published
2020

30. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Author

Hawryluk, Gregory WJ, Aguilera, Sergio, Buki, Andras, Bulger, Eileen, Citerio, Giuseppe, Cooper, D Jamie, Arrastia, Ramon Diaz, Diringer, Michael, Figaji, Anthony, Gao, Guoyi, Geocadin, Romergryko, Ghajar, Jamshid, Harris, Odette, Hoffer, Alan, Hutchinson, Peter, Joseph, Mathew, Kitagawa, Ryan, Manley, Geoffrey, Mayer, Stephan, Menon, David K, Meyfroidt, Geert, Michael, Daniel B, Oddo, Mauro, Okonkwo, David, Patel, Mayur, Robertson, Claudia, Rosenfeld, Jeffrey V, Rubiano, Andres M, Sahuquillo, Juan, Servadei, Franco, Shutter, Lori, Stein, Deborah, Stocchetti, Nino, Taccone, Fabio Silvio, Timmons, Shelly, Tsai, Eve, Ullman, Jamie S, Vespa, Paul, Videtta, Walter, Wright, David W, Zammit, Christopher, and Chesnut, Randall M

Subjects
Humans, Intracranial Hypertension, Monitoring, Physiologic, Algorithms, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Consensus Development Conferences as Topic, Practice Guidelines as Topic, Brain Injuries, Traumatic, Algorithm, Brain injury, Consensus, Head trauma, Intracranial pressure, Protocol, SIBICC, Seattle, Tiers, Traumatic Brain Injury (TBI), Neurosciences, Traumatic Head and Spine Injury, Brain Disorders, Physical Injury - Accidents and Adverse Effects, Clinical Sciences, Public Health and Health Services, Emergency & Critical Care Medicine
Abstract

BackgroundManagement algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation's sTBI Management Guidelines, as they were not evidence-based.MethodsWe used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists' decision tendencies were the focus of recommendations.ResultsWe provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination.ConclusionsOur modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.

Published
2019

31. Imaging biomarkers of posttraumatic epileptogenesis

Author

Garner, Rachael, La Rocca, Marianna, Vespa, Paul, Jones, Nigel, Monti, Martin M, Toga, Arthur W, and Duncan, Dominique

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Traumatic Head and Spine Injury, Physical Injury - Accidents and Adverse Effects, Neurodegenerative, Brain Disorders, Traumatic Brain Injury (TBI), Epilepsy, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Injuries and accidents, Anticonvulsants, Brain Injuries, Traumatic, Epilepsy, Post-Traumatic, Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, Tomography, X-Ray Computed, biomarkers, imaging, MRI, posttraumatic epilepsy, traumatic brain injury, MRI, Neurology & Neurosurgery, Clinical sciences
Abstract

Traumatic brain injury (TBI) affects 2.5 million people annually within the United States alone, with over 300 000 severe injuries resulting in emergency room visits and hospital admissions. Severe TBI can result in long-term disability. Posttraumatic epilepsy (PTE) is one of the most debilitating consequences of TBI, with an estimated incidence that ranges from 2% to 50% based on severity of injury. Conducting studies of PTE poses many challenges, because many subjects with TBI never develop epilepsy, and it can be more than 10 years after TBI before seizures begin. One of the unmet needs in the study of PTE is an accurate biomarker of epileptogenesis, or a panel of biomarkers, which could provide early insights into which TBI patients are most susceptible to PTE, providing an opportunity for prophylactic anticonvulsant therapy and enabling more efficient large-scale PTE studies. Several recent reviews have provided a comprehensive overview of this subject (Neurobiol Dis, 123, 2019, 3; Neurotherapeutics, 11, 2014, 231). In this review, we describe acute and chronic imaging methods that detect biomarkers for PTE and potential mechanisms of epileptogenesis. We also describe shortcomings in current acquisition methods, analysis, and interpretation that limit ongoing investigations that may be mitigated with advancements in imaging techniques and analysis.

Published
2019

32. Diagnostic performance of point-of-care ubiquitin carboxy-terminal Hydrolase-L1 assay in distinguishing imaging abnormalities in traumatic brain injury: A TRACK-TBI cohort study

Author

Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M. Ross, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura, Palacios, Eva, Perl, Daniel, Rabinowitz, Miri, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Zafonte, Ross, Wang, Kevin K., Munoz-Pareja, Jennifer C., Lautenslager, Lauren A., Tyndall, J. Adrian, Yang, Zhihui, Kerrigan, Maria R., Diaz-Arrastia, Ramon, Korley, Frederick K., Okonkwo, David, Puccio, Ava M., Yue, John K., Taylor, Sabrina R., Mukherjee, Pratik, Yuh, Esther L., Temkin, Nancy R., Robertson, Claudia S., Sun, Xiaoying, Jain, Sonia, Markowitz, Amy J., and Manley, Geoffrey T.

Published
2023
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35. Hemorrhage Expansion Rates Before and After Minimally Invasive Surgery for Intracerebral Hemorrhage: Post Hoc Analysis of MISTIE II/III

Author

Ziai, Wendy C., primary, Badihian, Shervin, additional, Ullman, Natalie, additional, Thompson, Carol B., additional, Hildreth, Meghan, additional, Piran, Pirouz, additional, Montano, Nataly, additional, Vespa, Paul, additional, Martin, Neil, additional, Zuccarello, Mario, additional, Mayo, Steven W., additional, Awad, Issam, additional, and Hanley, Daniel F., additional

Published
2024
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36. Brain Extraction from Normal and Pathological Images: A Joint PCA/Image-Reconstruction Approach

Author

Han, Xu, Kwitt, Roland, Aylward, Stephen, Bakas, Spyridon, Menze, Bjoern, Asturias, Alexander, Vespa, Paul, Van Horn, John, and Niethammer, Marc

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Brain extraction from images is a common pre-processing step. Many approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images with strong pathologies, for example, the presence of a tumor or of a traumatic brain injury, is challenging. In such cases, tissue appearance may deviate from normal tissue and violates algorithmic assumptions for these approaches; hence, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis, (2) pathologies are captured via a total variation term, and (3) non-brain tissue is captured by a sparse term. Decomposition and image registration steps are alternated to allow statistical modeling in a fixed atlas space. As a beneficial side effect, the model allows for the identification of potential pathologies and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our method on four datasets: the IBSR and LPBA40 datasets which show normal images, the BRATS dataset containing images with brain tumors and a dataset containing clinical TBI images. We compare the performance with other popular models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing methods on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction on a wide variety of images.

Published
2017
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37. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis

Author

Wilson, Michael R, Sample, Hannah A, Zorn, Kelsey C, Arevalo, Shaun, Yu, Guixia, Neuhaus, John, Federman, Scot, Stryke, Doug, Briggs, Benjamin, Langelier, Charles, Berger, Amy, Douglas, Vanja, Josephson, S Andrew, Chow, Felicia C, Fulton, Brent D, DeRisi, Joseph L, Gelfand, Jeffrey M, Naccache, Samia N, Bender, Jeffrey, Dien Bard, Jennifer, Murkey, Jamie, Carlson, Magrit, Vespa, Paul M, Vijayan, Tara, Allyn, Paul R, Campeau, Shelley, Humphries, Romney M, Klausner, Jeffrey D, Ganzon, Czarina D, Memar, Fatemeh, Ocampo, Nicolle A, Zimmermann, Lara L, Cohen, Stuart H, Polage, Christopher R, DeBiasi, Roberta L, Haller, Barbara, Dallas, Ronald, Maron, Gabriela, Hayden, Randall, Messacar, Kevin, Dominguez, Samuel R, Miller, Steve, and Chiu, Charles Y

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Infectious Diseases, Clinical Research, Biotechnology, Brain Disorders, Rare Diseases, Infection, Good Health and Well Being, Adolescent, Adult, Cerebrospinal Fluid, Child, Child, Preschool, Encephalitis, Female, Genome, Microbial, High-Throughput Nucleotide Sequencing, Humans, Infant, Infections, Length of Stay, Male, Meningitis, Meningoencephalitis, Metagenomics, Middle Aged, Myelitis, Prospective Studies, Sequence Analysis, DNA, Sequence Analysis, RNA, Young Adult, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundMetagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test.MethodsIn a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review.ResultsWe enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment.ConclusionsRoutine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).

Published
2019

38. The Temporal Relationship of Mental Health Problems and Functional Limitations following mTBI: A TRACK-TBI and TED Study

Author

Zahniser, Evan, Nelson, Lindsay D, Dikmen, Sureyya S, Machamer, Joan E, Stein, Murray B, Yuh, Esther, Manley, Geoffrey T, Temkin, Nancy R, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Ross Bullock, M, Chesnut, Randall, Corrigan, John D, Crawford, Karen, Diaz-Arrastia, Ramon, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam, Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Claude Hemphill, J, Hotz, Gillian, Jain, Sonia, Korley, Frederick, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Noel, Florence, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Taylor, Sabrina, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Wang, Kevin, Yue, John, and Zafonte, Ross

Subjects
Behavioral and Social Science, Depression, Mental Health, Biomedical Imaging, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Traumatic Head and Spine Injury, Neurosciences, Traumatic Brain Injury (TBI), Clinical Research, 6.6 Psychological and behavioural, Evaluation of treatments and therapeutic interventions, Mental health, Injuries and accidents, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Anxiety, Brain Concussion, Female, Humans, Longitudinal Studies, Male, Middle Aged, Recovery of Function, Time Factors, Young Adult, brain injuries, mental health, patient outcome assessment, traumatic, TRACK-TBI Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

Mental health problems, such as depression and anxiety, are often associated with functional limitations after traumatic brain injury (TBI), prompting researchers to explore which of these TBI-related sequelae tends to precede the other. Past studies among patients with injuries ranging in severity have predominantly reported that functional impairments predict subsequent psychological concerns, rather than the other way around; however, it remains unclear whether this directionality holds for individuals with mild TBI (mTBI). The present study utilized a cross-lagged panel design within a structural equation modeling analytical framework to explore the longitudinal relationships of symptoms of depression and anxiety to functional status among 717 adult mTBI patients, with assessments occurring at 2 weeks and 3 months post-injury. Symptoms of both depression and anxiety significantly predicted subsequent functional limitations (λs = -0.21 and -0.25), whereas the reverse effects were nonsignificant (λs = -0.05 and -0.03); thus, psychological concerns appeared to function as a precursor to functional impairment. This pattern was particularly pronounced among patients with normal head computed tomography (CT) results; however, results were less clear cut among those subjects whose injuries were accompanied by intracranial abnormalities detected on CT imaging, suggesting the possibility of a more reciprocal relationship in the case of CT-positive mTBI. These results may serve to partially explain the incidence of persistent functional limitations observed among subsets of mTBI patients in past studies. Findings likewise highlight the importance of assessment and treatment for mental health problems after mTBI as an important factor to promote psychological well-being and functional recovery.

Published
2019

39. Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study

Author

Tubi, Meral A, Lutkenhoff, Evan, Blanco, Manuel Buitrago, McArthur, David, Villablanca, Pablo, Ellingson, Benjamin, Diaz-Arrastia, Ramon, Van Ness, Paul, Real, Courtney, Shrestha, Vikesh, Engel, Jerome, and Vespa, Paul M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Physical Injury - Accidents and Adverse Effects, Neurodegenerative, Traumatic Head and Spine Injury, Biomedical Imaging, Traumatic Brain Injury (TBI), Neurosciences, Epilepsy, Brain Disorders, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Adult, Brain Injuries, Traumatic, Epilepsy, Post-Traumatic, Female, Humans, Longitudinal Studies, Male, Prospective Studies, Severity of Illness Index, Temporal Lobe, Brain trauma, Post-traumatic epilepsy, Coma, Seizures, Brain atrophy, Status epilepticus, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract

ObjectiveInjury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE.MethodsWe assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury.ResultsEarly seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p

Published
2019

40. The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol

Author

Vespa, Paul M, Shrestha, Vikesh, Abend, Nicholas, Agoston, Denes, Au, Alicia, Bell, Michael J, Bleck, Thomas P, Blanco, Manuel Buitrago, Claassen, Jan, Diaz-Arrastia, Ramon, Duncan, Dominique, Ellingson, Ben, Foreman, Brandon, Gilmore, Emily J, Hirsch, Lawrence, Hunn, Martin, Kamnaksh, Alaa, McArthur, David, Morokoff, Andrew, O'Brien, Terrence, O'Phelan, Kristine, Robertson, Courtney L, Rosenthal, Eric, Staba, Richard, Toga, Arthur, Willyerd, Frederick A, Zimmermann, Lara, Yam, Elisa, Martinez, Susana, Real, Courtney, and Engel, Jerome

Subjects
Biomedical and Clinical Sciences, Neurosciences, Precision Medicine, Clinical Research, Physical Injury - Accidents and Adverse Effects, Brain Disorders, Neurodegenerative, Epilepsy, Traumatic Head and Spine Injury, Traumatic Brain Injury (TBI), 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Good Health and Well Being, Biomarkers, Brain, Brain Injuries, Traumatic, Computational Biology, Epilepsy, Post-Traumatic, Humans, Longitudinal Studies, Observational Studies as Topic, Prospective Studies, Clinical Sciences, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.

Published
2019

41. Opposing CSF hydrodynamic trends found in the cerebral aqueduct and prepontine cistern following shunt treatment in patients with normal pressure hydrocephalus.

Author

Hamilton, Robert, Scalzo, Fabien, Baldwin, Kevin, Dorn, Amber, Vespa, Paul, Hu, Xiao, and Bergsneider, Marvin

Subjects
Aqueduct of Sylvius, Cerebral compliance, Cerebrospinal fluid (CSF), Normal pressure hydrocephalus, Phase contrast MRI (PC-MRI), Prepontine CISTERN, Aged, Aged, 80 and over, Cerebral Aqueduct, Cerebrospinal Fluid, Cerebrospinal Fluid Shunts, Female, Follow-Up Studies, Humans, Hydrocephalus, Normal Pressure, Hydrodynamics, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Pattern Recognition, Automated, Treatment Outcome
Abstract

BACKGROUND: This study investigated cerebrospinal fluid (CSF) hydrodynamics using cine phase-contrast MRI in the cerebral aqueduct and the prepontine cistern between three distinct groups: pre-shunt normal pressure hydrocephalus (NPH) patients, post-shunt NPH patients, and controls. We hypothesized that the hyperdynamic flow of CSF through the cerebral aqueduct seen in NPH patients was due to a reduction in cisternal CSF volume buffering. Both hydrodynamic (velocity, flow, stroke volume) and peak flow latency (PFL) parameters were investigated. METHODS: Scans were conducted on 30 pre-treatment patients ranging in age from 58 to 88 years along with an additional 12 controls. Twelve patients also received scans following either ventriculoatrial (VA) or ventriculoperitoneal (VP) shunt treatment (9 VP, 3 VA), ranging in age from 74 to 89 years with a mean follow up time of 6 months. RESULTS: Significant differences in area, velocity, flow, and stroke volume for the cerebral aqueduct were found between the pre-treatment NPH group and the healthy controls. Shunting caused a significant decrease in both caudal and cranial mean flow and stroke volume in the cerebral aqueduct. No significant changes were found in the prepontine cistern between the pre-treatment group and healthy controls. For the PFL, no significant differences were seen in the cerebral aqueduct between any of the three groups; however, the prepontine cistern PFL was significantly decreased in the pre-treatment NPH group when compared to the control group. CONCLUSIONS: Although several studies have quantified the changes in aqueductal flow between hydrocephalic groups and controls, few studies have investigated prepontine cistern flow. Our study was the first to investigate both regions in the same patients for NPH pre- and post- treatment. Following shunt treatment, the aqueductal CSF metrics decreased toward control values, while the prepontine cistern metrics trended up (not significantly) from the normal values established in this study. The opposing trend of the two locations suggests a redistribution of CSF pulsatility in NPH patients. Furthermore, the significantly decreased latency of the prepontine cisternal CSF flow suggests additional evidence for CSF pulsatility dysfunction.

Published
2019

42. pH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI)

Author

Ellingson, Benjamin M, Yao, Jingwen, Raymond, Catalina, Chakhoyan, Ararat, Khatibi, Kasra, Salamon, Noriko, Villablanca, J Pablo, Wanner, Ina, Real, Courtney R, Laiwalla, Azim, McArthur, David L, Monti, Martin M, Hovda, David A, and Vespa, Paul M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Bioengineering, Neurosciences, Traumatic Head and Spine Injury, Clinical Research, Biomedical Imaging, Physical Injury - Accidents and Adverse Effects, Traumatic Brain Injury (TBI), Brain Disorders, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Injuries and accidents, Adult, Aged, Brain Injuries, Traumatic, Echo-Planar Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Molecular Imaging, Protons, Young Adult, CEST, pH imaging, Traumatic brain injury, TBI, Biological psychology, Clinical and health psychology
Abstract

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTRasym at 3 ppm) in areas of T2 hyperintensity or edema (P

Published
2019

45. Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study

Author

Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubović, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Nair, Nandesh, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Oresic, Matej, Ortolano, Fabrizio, Otesile, Olubukola, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rehorčíková, Veronika, Retel Helmrich, Isabel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Kowark, Ana, Stevens, Robert, Stewart, William, Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolijn, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, Van der Jagt, Mathieu, van der Naalt, Joukje, Van der Steen, Gregory, van Dijck, Jeroen T.J.M., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Van Veen, Ernest, van Wijk, Roel, Vande Vyvere, Thijs, Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K.W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Zeiler, Frederick A., Ziverte, Agate, Zoerle, Tommaso, van Essen, Thomas A, Lingsma, Hester F, Pisică, Dana, Singh, Ranjit D, Volovici, Victor, den Boogert, Hugo F, Younsi, Alexander, Peppel, Lianne D, Heijenbrok-Kal, Majanka H, Ribbers, Gerard M, Walchenbach, Robert, Menon, David K, Hutchinson, Peter, Depreitere, Bart, Steyerberg, Ewout W, Maas, Andrew I R, de Ruiter, Godard C W, and Peul, Wilco C

Published
2022
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46. A genome-wide association study of outcome from traumatic brain injury

Author

Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan P., Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J.A., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Jiyao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, LarsOwe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I.R., CastañoLeón, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David K., Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia F.J., Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, JeanFrançois, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, SanchezPorras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T.J.M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, Vyvere, Thijs Vande, van Wijk, Roel P.J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K.W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Izzy, Saef, Radmanesh, Farid, Frantzén, Janek, Katila, Ari, Maanpää, Henna-Rikka, Tallus, Jussi, Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Barber, Jason, Bodien, Yelena, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Goldman, Dana, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, Claude, Hotz, Gillian, Jain, Sonia, Keene, Dirk, Korley, Frederick K., Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Manley, Geoffrey T., Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B, Noel, Florence, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Taylor, Sabrina, Temkin, Nancy, Toga, Arthur, Valadka, Alex, Vassar, Mary, Yue, John K., Yuh, Esther, Zafonte, Ross, Kals, Mart, Kunzmann, Kevin, Parodi, Livia, Anderson, Christopher D., Puccio, Ava M., Okonkwo, David O., Stein, Murray B., and Manley, Geoff T.

Published
2022
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47. Lesion Normalization and Supervised Learning in Post-traumatic Seizure Classification with Diffusion MRI

Author

Akbar, Md Navid, Ruf, Sebastian, La Rocca, Marianna, Garner, Rachael, Barisano, Giuseppe, Cua, Ruskin, Vespa, Paul, Erdoğmuş, Deniz, Duncan, Dominique, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Cetin-Karayumak, Suheyla, editor, Christiaens, Daan, editor, Figini, Matteo, editor, Guevara, Pamela, editor, Gyori, Noemi, editor, Nath, Vishwesh, editor, and Pieciak, Tomasz, editor

Published
2021
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48. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Author

Ackerlund, Cecilia, Adams, Hadie, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Castaño-León, Ana M., Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Clusmann, Hans, Coburn, Mark Steven, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Covic, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maegele, Marc, Majdan, Marek, Manara, Alex, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McFadyen, Charles, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Oresic, Matej, Ortolano, Fabrizio, Otesile, Olubukola, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rehorčíková, Veronika, Retel Helmrich, Isabel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosenfeld, Jeffrey, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolijn, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, van der Jagt, Mathieu, van der Naalt, Joukje, Van der Steen, Gregory, van Dijck, Jeroen T.J.M., van Erp, Inge A., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Veen, Ernest, van Wijk, Roel, Vande Vyvere, Thijs, Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Peter, Wang, Kevin K.W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Ziverte, Agate, Zoerle, Tommaso, Adeoye, Opeolu, Badjatia, Neeraj, Barber, Jason, Bergin, Michael, Boase, Kim, Bodien, Yelena, Chesnut, Randall, Corrigan, John, Crawford, Karen, Diaz-Arrastia, Ramon, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, Venkata, Ferguson, Adam R, Foreman, Brandon, Gaudette, Etienne, Giacino, Joseph, Gonzalez, Luis, Gopinath, Shankar, Grandhi, Ramesh, Gullapalli, Rao, Hemphill, Claude, Hotz, Gillian, Huie, Russell, Jha, Ruchira, Keene, C. Dirk, Kitagawa, Ryan, Korley, Frederick, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Mukherjee, Pratik, Nelson, Lindsay, Ngwenya, Laura B., Noel, Florence, Nolan, Amber, Okonkwo, David, Palacios, Eva, Perl, Daniel, Puccio, Ava, Rabinowitz, Miri, Robertson, Claudia, Rodgers, Richard Ben, Rosand, Jonathan, Rosenthal, Eric, Sander, Angelle, Sandsmark, Danielle, Sugar, Gabriella, Schneider, Andrea, Schnyer, David, Seabury, Seth, Sherer, Mark, Stein, Murray, Temkin, Nancy, Toga, Arthur, Torres-Espin, Abel, Valadka, Alex, Vassar, Mary, Wang, Kevin, Wang, Vincent, Yue, John K., Yuh, Esther, Zafonte, Ross, Galimberti, Stefania, Graziano, Francesca, Maas, Andrew I R, Isernia, Giulia, Lecky, Fiona, Jain, Sonia, Sun, Xiaoying, Gardner, Raquel C, Taylor, Sabrina R, Markowitz, Amy J, Manley, Geoffrey T, Valsecchi, Maria Grazia, Bellelli, Giuseppe, and Citerio, Giuseppe

Published
2022
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49. Neurocognitive correlates of probable posttraumatic stress disorder following traumatic brain injury

Author

Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Ceyisakar, Iris, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Koraropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I.R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Synnot, Anneliese, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T.J.M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P.J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K.W., Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Van Praag, Dominique L.G., Wouters, Kristien, and Van Den Eede, Filip

Published
2022
Full Text
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